# US 10,500,230 B2 · Kidney-derived cells and methods of use in tissue repair and regeneration

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- Number: US 10,500,230 B2
- Document ID: US10500230B2
- Status: Granted
- Kind: B2
- Application number: 11/871,045
- Filed: 2007-10-11
- Published: 2008-05-15
- Granted: 2019-12-10
- Earliest claimed: 2006-10-12
- Assignees: DePuy Synthes Products, Inc.
- Applicants: David C. Colter; Agnieszka Seyda; Charito S. Buensuceso; Anna Gosiewska
- Inventors: David C. Colter; Agnieszka Seyda; Charito S. Buensuceso; Anna Gosiewska
- Web page: https://patentgrep.com/patent/US10500230B2

## CPC

- A61K 35/22: Urine; Urinary tract, e.g. kidney or bladder; Intraglomerular mesangial cells; Renal mesenchymal cells; Adrenal gland
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 13/12: of the kidneys
- C12N 5/0686: {Kidney cells}
- C12N 5/0687: {Renal stem cells; Renal progenitors}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- C12N 2533/40: Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Isolated or purified mammalian kidney-derived cell populations from mammalian kidney tissue are provided. Methods are provided for the isolation and purification of the mammalian kidney-derived cell population. Methods for treating kidney disease are provided by administration of the isolated or purified mammalian kidney-derived cell population to a mammalian subject.

## Claims

### Claim 1

An implant comprising a thawed human kidney cell population derived from single cell clones, wherein said cell population is capable of self-renewal and expansion in culture, is positive for expression of HLA-I and CD44 and at least one of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, EpoR, BMP2, BMP7, or GDF5, and is negative for the expression of CD133, E-cadherin, and Wnt-4 and at least one of Sox2, FGF4, hTert, SIX2 or GATA-4; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

### Claim 2 (depends on 1)

The implant of claim 1, wherein the cell population is positive for at least one of cell-surface markers CD24, CD29, CD49c, CD73, CD90, CD166, or SSEA-4, and negative for at least one of cell-surface markers HLA II, CD31, CD34, CD45, CD56, CD80, CD86, CD104, CD105, CD117, CD138, or CD141.

### Claim 3 (depends on 1)

The implant of claim 1, wherein the cells are derived from kidney cortex.

### Claim 4

An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of at least one of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, EpoR, BMP2, BMP7, or GDF5 and negative for the expression of at least one of Sox2, FGF4, hTert, Wnt-4, SIX2 or GATA-4 wherein the cell population secretes at least one of trophic factors FGF2, HGF, TGFα, TIMP-1, TIMP-2, MMP-2 or VEGF and does not secrete at least one of trophic factors PDGF-bb or IL12p70; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

### Claim 5 (depends on 1)

The implant of claim 1, wherein the cell population comprises kidney progenitor cells.

### Claim 6

An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of at least one of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, EpoR, BMP2, BMP7, or GDF5 and negative for the expression of at least one of Sox2, FGF4, hTert, Wnt-4, SIX2 or GATA-4, wherein the cell population comprises kidney progenitor cells, and wherein the kidney progenitor cells are capable of differentiating to adipocytes or osteoblasts; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

### Claim 7

An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, and EpoR and negative for the expression of at least one of Sox2, FGF4, hTert, Wnt-4, SIX2 and GATA-4; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

### Claim 8

An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, Eya1, HNF3B, CXC-R4, Sox-17, and EpoR, negative for the expression of at least one of Sox2, FGF4, hTert, Wnt-4, SIX2 and GATA-4; positive for cell-surface markers HLA I, CD24, CD29, CD44, CD49c, CD73, CD90, CD166, and SSEA-4; and negative for cell-surface markers HLA II, CD31, CD34, CD45, CD56, CD80, CD86, CD104, CD105, CD117, CD133, CD138, CD141, and E-cadherin; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

### Claim 9

An implant comprising a thawed human kidney cell population derived from single cell clones, said cell population capable of self-renewal and expansion in culture, wherein the cell population is positive for expression of Oct-4, Rex-1, Pax-2, Cadherin-11, FoxD1, WT1, EpoR, BMP2, BMP7, and GDF5, and negative for the expression of Sox2, FGF4, and hTert; and a matrix comprising a biocompatible polymer, wherein the cell population is seeded on the matrix, and wherein said cell population was cryopreserved in a medium containing dimethylsulfoxide (DMSO) prior to thawing.

### Claim 10 (depends on 9)

The implant of claim 9, wherein the cell population is positive for cell-surface markers CD24, CD29, CD44, CD49c, CD73, CD90, CD166, and SSEA-4; and negative for cell-surface markers CD31, CD34, CD45, CD56, CD104, CD105, CD117, CD133, CD138, CD141, and E-cadherin.

### Claim 11 (depends on 1)

The implant of claim 1, wherein said biocompatible polymer is synthetic.

### Claim 12 (depends on 11)

The implant of claim 11, wherein said synthetic polymer is selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

### Claim 13 (depends on 11)

The implant of claim 11, wherein said biocompatible synthetic polymer is a polyester.

### Claim 14 (depends on 13)

The implant of claim 13, wherein the polyester is selected from the group consisting of homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

### Claim 15 (depends on 4)

The implant of claim 4, wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

### Claim 16 (depends on 6)

The implant of claim 6, wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

### Claim 17 (depends on 7)

The implant of claim 7, wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

### Claim 18 (depends on 8)

The implant of claim 8, wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

### Claim 19 (depends on 9)

The implant of claim 9, wherein said biocompatible polymer is a synthetic polymer selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylene oxalates, polyamides, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, homopolymers and copolymers of lactide (which includes lactic acid, d-, 1- and meso lactide), glycolide (including glycolic acid), epsilon-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, delta-valerolactone, beta-butyrolactone, gamma-butyrolactone, epsilon-decalactone, hydroxybutyrate (repeating units), hydroxyvalerate (repeating units), 1,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6-dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pivalolactone, alpha, alpha-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof.

### Claim 20 (depends on 1)

The implant of claim 1, wherein the cells form a monolayer on the matrix.